Risk Factors For Stage Research Articles

Optimal cut-off value for lymph node harvesting in colon cancer based on tumor stage and sidedness: A retrospective analysis of a Japanese nationwide cohort.

149 Background: The presence of fewer than 12 harvested lymph nodes (LN) is currently considered a risk factor in stage II colon cancer (CC). However, this cut-off value does not take into consideration the biological differences associated with tumor sidedness. Moreover, the applicability of this cut-off value to stage III CC is unknown. Methods: Patients with pathological stage II/III CC who underwent curative surgical resection were assessed using data from the Japanese Society for Cancer of the Colon and Rectum database (2001–2015). The optimal cut-off value of harvested LN was evaluated by analyzing all cut-off values (i.e., 3–40), taking into account the point estimate of the hazard ratio (HR) and lower limit of the 95% confidence interval (CI), according to the tumor stage (II/III) and sidedness (right/left). A Cox proportional hazards model was used to investigate the impact of the number of harvested LN on overall survival, adjusting for age, sex, T stage, histology, size of tumor, sidedness, adjuvant chemotherapy and extent of colon resection. Multivariate analysis was also conducted. Results: From the data, 4249 (left/right; 3248/1001) and 3549 (left/right; 2798/751) patients with stage II and III CC, respectively, were identified. The median number of harvested LN was identical between stage II (18, interquartile range [IQR] (12–15)) and III (18, IQR (13–25)). However, this number was higher in right-sided CC (21, IQR (14–31)) versus left-sided CC (17, IQR (12–24)). In stage II, the conventional cut-off value (i.e., 12 LN) was identified as a prognostic factor in the multivariate analysis (HR 1.45; 95% CI: 1.20–1.75; p<0.001). Nevertheless, the prognostic impact of the number of harvested LN was stronger when the optimal cut-off value was set to 7 (HR 1.88; 95% CI: 1.44–2.44; p<0.001). In stage III, the optimal cut-off value was 12 (HR 1.88; 95% CI: 1.44–2.44; p<0.001). When evaluated based on tumor sidedness, the optimal cut-off value differed, especially for stage III. Data are shown in the table. Similar results were obtained following the exclusion of the extent of bowel resection as variable in Multivariate analysis. Conclusions: While the presence of 12 harvested LNs remains a valid prognostic factor, the optimal cut-off value can be further evaluated based on tumor stage and sidedness. Stage II Stage III All Left Right All Left Right Cut-off value 12 12 12 12 12 12 N(>cut-off/<cut-off) 3209/1040 2371/877 838/163 2814/735 2181/617 633/118 HR(>cut-off/<cut-off)(95% CI) 1.45 (1.20-1.75) 1.49 (1.20-1.84) 1.31 (0.85-2.02) 1.30 (1.09-1.55) 1.27 (1.05-1.54) 1.43 (0.97-2.13) P value <0.001 <0.001 0.216 <0.003 0.015 0.073 Cut-off value 7 7 10 20 13 N(>cut-off/<cut off) 3930/319 2977/271 889/112 1200/1598 609/142 HR(>cut-off/<cut-off)(95% CI) 1.88 (1.44-2.44) 2.07 (1.56-2.74) 1.39 (0.84-2.27) 1.35 (1.13-1.60) 1.59 (1.11-2.28) P value <0.001 <0.001 0.198 <0.001 0.011

UBE2T promotes stage I lung adenocarcinoma progression through PBX1 ubiquitination and PBX1/RORA regulation

BackgroundPost-translational modification pathway of protein ubiquitination is intricately associated with tumorigenesis. We previously reported elevated ubiquitin-conjugating enzyme 2T (UBE2T) as an independent risk factor in stage I lung adenocarcinoma and promoting cellular proliferation. However, its underlying mechanisms needed further investigation.MethodsImmunohistochemistry was used to assess the expression of UBE2T and retinoic acid receptor-related orphan receptor α (RORA) in stage I LUAD. Cell proliferation, migration, and invasion of LUAD cell lines were measured by Cell Counting Kit-8 assay (CCK-8), Colony-forming assay and Transwell assay, respectively. Western blot analysis was performed to determine the expression of epithelial-mesenchymal transition (EMT) markers. A xenograft model was established to evaluate the proliferative capacity of UBE2T and its interaction with RORA in promoting LUAD. Mechanistic insights into the promotion of early-stage LUAD by UBE2T were obtained through luciferase reporter assay, chromatin immunoprecipitation and co-immunoprecipitation.ResultsUBE2T and RORA expression was significantly up- and down-regulated in early-stage LUAD patients which’s proved to be associated with unfavorable outcomes, strengthened cell proliferation, migration, EMT and invasion through its interaction with RORA both in vivo and in vitro. The growth NSCLC xenografts was reduced by down-expression of UBE2T but was suppressed by RORA knockout. Mechanistically, UBE2T mediated the ubiquitination of the intermediate transcription factor PBX1, which played a transcriptional role in downstream regulation of RORA.ConclusionThe oncogenic role of UBE2T and the UBE2T-PBX1-RORA axis in driving malignant progression in Stage I LUAD had been established. UBE2T might be a novel and promising therapeutic target for LUAD treatment.

Cumulative incidence and risk factors for medication-related osteonecrosis of the jaw during long-term prostate cancer management

Bone-modifying agents (BMA) are extensively used in treating patients with prostate cancer with bone metastases. However, this increases the risk of medication-related osteonecrosis of the jaw (MRONJ). The safety of long-term BMA administration in clinical practice remains unclear. We aimed to determine the cumulative incidence and risk factors of MRONJ. One hundred and seventy-nine patients with prostate cancer with bone metastases treated with BMA at our institution since 2008 were included in this study. Twenty-seven patients (15%) had MRONJ during the follow-up period (median, 19 months; interquartile range, 9–43 months). The 2-year, 5-year, and 10-year cumulative MRONJ incidence rates were 18%, 27%, and 61%, respectively. Multivariate analysis identified denosumab use as a risk factor for MRONJ, compared with zoledronic acid use (HR 4.64, 95% CI 1.93–11.1). Additionally, BMA use at longer than one-month intervals was associated with a lower risk of MRONJ (HR 0.08, 95% CI 0.01–0.64). Furthermore, six or more bone metastases (HR 3.65, 95% CI 1.13–11.7) and diabetes mellitus (HR 5.07, 95% CI 1.68–15.2) were risk factors for stage 2 or more severe MRONJ. MRONJ should be considered during long-term BMA administration in prostate cancer patients with bone metastases.

The impact of tumor size on the prognosis and chemotherapy efficacy in stage I/II colon cancer patients.

Background: The impact of tumor size on the survival and chemotherapy reponse of early-stage colon cancer remains unclear. Our study explored the effect of tumor size on overall survival (OS) and postoperative chemotherapy efficacy in patients with stage I/II colon cancer. Methods: Stage I/II colon cancer patients from the Surveillance, Epidemiology and End Results (SEER) database and a China center were extracted as two cohorts respectively. X-tile program was adopted to acquire optimal cutoff points of tumor size (16mm and 49mm). Harrell's concordance index (c-index) and time-dependent receiver operating characteristic curve (ROC) were used to indicate discrimination ability of prognostic factors. Results: Overall, 104,908 and 168 stage I/II postoperative colon cancer patients from SEER database and a China center were eligible, respectively. Kaplan-Meier analysis showed that large tumor size was associated with poor OS in two cohorts. The effect of tumor size on OS gradually decreased as the T stage increased both before PSM (c-index 0.535 for T1N0M0 and 0.506 for T4N0M0, p<0.05) and after PSM (c-index 0.543 for T1N0M0, p<0.05; c-index 0.543 for T4N0M0, p>0.05). Stratified analyses showed that chemotherapy improved the OS rate by 9.5% (chemotherapy vs. non-chemotherapy: 83.5% vs. 73.0%) or 12.8% (chemotherapy vs. non-chemotherapy: 85.7% vs. 72.9%) before and after PSM in T2N0M0 patients with tumor size >49 mm, but not in T1N0M0. The survival benefit provided by chemotherapy for T2N0M0 patients with large tumor was also validated in the Chinese cohort. Conclusions: Large tumor size was a risk factor for stage I/II colon cancer, especially for T1N0M0. Tumor size could serve as a complementary factor guiding postoperative chemotherapy for T2N0M0 patients.

The stage-dependent prognostic role of ARID1A in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death. Although novel treatment currently achieves a better response, the majority of HCC patients develop resistance and cannot benefit. Hence, novel biomarkers for guiding therapy and predicting the prognosis are needed. Tissue microarrays of 206 HCC patients were used, and ARID1A expression was determined by immunohistochemistry. Databases were used for the verification and expansion of our results. The "rms" package of R software was used for the construction of the nomogram. ARID family alterations were associated with disease-free survival (P=0.0325) and overall survival (OS) (P=0.0076). Subgroup analysis confirmed the prognostic effect of ARID1A, ARID1B, and ARID2 alterations. In addition, ARID family genomic alterations, especially ARID1A, were closely related to poor progression-free survival (ARID: P=0.0011; ARID1A: P=0.0082) and OS (ARID: P=0.0161; ARID1A: P=0.0220) after sorafenib treatment. ARID1A expression was found to display a stage-dependent effect on the prognosis, serving as a risk factor in stage I-II patients (P<0.0001) and a protective factor in stage III-IV patients (P=0.0180). ARID1A has dual roles in HCC in a tumor stage-dependent manner, and further study is required to uncover the complex function of ARID1A in HCC development, disease progression, and therapy.

Prognosis of carcinoembryonic antigen (CEA) in stage I colorectal adenocarcinoma and development of a prediction model: a retrospective study based on the SEER database.

To investigate the prognostic significance of preoperative carcinoembryonic antigen (CEA) status in stage I colorectal classical adenocarcinoma (CCA) and mucinous adenocarcinoma (MUC), and to construct a nomogram model of stage I CCA. The SEER database was used to collect 14,226 patients diagnosed with stage I colorectal adenocarcinoma (CA) from 2010 to 2015. The prognostic significance of preoperative CEA status in stage I CA and MUC was examined by propensity-matching score (PSM). We analyzed the factors affecting the prognosis of patients with stage I CCA, and constructed and verified the prognostic model. After PSM, the cancer-specific survival rate (CCS) of CEA-positive patients in stage T1 and T2 CCA was significantly lower than that of CEA-negative patients in stage T1 and T2 [HR = 0.37 (0.29-0.48), P < 0.001], [HR = 0.52 (0.41-0.65), P < 0.001]. However, there was no significant difference in CSS between CEA-positive and CEA-negative patients in T1 and T2 MUC [HR = 0.58 (0.43-0.79), P = 0.096], [HR = 0.76 (0.36-1.62), P = 0.477]. A nomogram was constructed based on the results of the multivariate COX regression model. Based on the AUC of ROC analysis, calibration plot and decision curve analysis (DCA), we concluded that the risk and prognosis model of CCA showed excellent performance. Elevated CEA is a risk factor for stage I CCA, but not for MUC. And the nomogram is accurate enough to predict the risk and prognostic factors of CCA.

Brief report: risk stratification following curative therapy for stage I NSCLC.

Surveillance with computed tomography (CT) imaging following curative treatment of stage I non-small cell lung cancer (NSCLC) is important to identify recurrence or second primary lung cancers (SPLC). The pattern and risks of recurrence following curative therapy and optimal duration of surveillance scans remain unknown. The objective of our study is to assess the pattern of recurrence and development of SPLC to risk stratify patients with stage I NSCLC following curative therapy. We identified 261 patients who received curative therapy for stage I NSCLC at Mayo Clinic Florida. Data was collected on clinical and demographic features including gender, smoking history, stage, treatment, histologic subtype, and tumor grade. Kaplan-Meier method was used to evaluate the disease free survival (DFS). Cox proportional hazard model was used to identify risk factors for recurrence. Negative tobacco history and stage IA tumors were associated with significantly prolonged DFS after adjusting for co-variates (p=0.001 and p=0.005). Univariate Cox proportional hazards model identified tobacco history and stage 1B as risk factors for recurrence with unadjusted hazard ratio (HR) of 2.8 and 2.0, respectively. After adjusting for covariates, only stage IB was statistically significant predictor of recurrence with a hazard ratio of 2.1 (Confidence Interval (CI) 95% 1.2-3.6; p=0.007). An individualized approach that considers risk factors of stage and smoking history may be useful in determining whether to continue annual CT surveillance after five years post curative therapy for stage I NSCLC.

The Prognostic Role of Mismatch Repair Status and CDX-2 Expression with Inflammatory Markers and Pathological Risk Factors in Stage II and III Colon Cancer: Multicenter Real-Life Data.

Colorectal cancer is common worldwide, and adjuvant treatment's benefit is still controversial. We designed this study to determine the role of MSI and CDX-2 status determined by immunohistochemistry (IHC) combined with the inflammatory markers and pathological parameters in predicting disease recurrence in stage II and III colon cancer. A total of 226 stage II/III colon cancer patients with a median age of 59years who underwent initial surgery were included in this retrospective study. The pathologic assessment of MSI and CDX-2 was performed twice by immunohistochemistry (IHC) and two different pathologists. No staining/weak staining below 10% of the tumor was accepted as CDX-2 negative, and any MSI clones with weak staining below 10% were accepted as MSI-H. The laboratory parameters were noted at the initial diagnosis. One hundred twenty-one and 105 patients were diagnosed with stage III and II colon cancer. 58.0% of patients were male, 46 (20.4%) of tumor tissue were MSS, and 17 (7.5%) were CDX-2 negative. One hundred twenty-nine tumors were localized in the right colon. Disease recurrence was significantly correlated with tumor localization, CDX-2 status, stage at diagnosis, and preoperatively median CRP and CEA levels. DFS rates for MSS patients with CDX-2 negative and positive were 36.7% and 98.1%, respectively [p < 0.001]. There was no significant correlation between MSI status and CDX-2 status. MSI status, the presence of adjuvant treatment, and systemic inflammatory markers were not significant prognostic factors for DFS. CDX-2 status [HR:0.08, CI 95% 0.03-0.17, p < 0.001 HR: 1.7, CI 95% 1.1-3.0, p = 0.03], disease stage [HR:2.6, CI 95% 1.43-4.74], and preoperatively CEA levels [HR:4.1 CI 95% 2.18-785, p < 0.001 were independent significant prognostic factors for DFS. CDX-2 loss was an independent prognostic factor for DFS and disease recurrence in early-stage colon cancer. MSS patients with CDX-2 loss had significantly worse survival outcomes, and this might be the reason for deciding on adjuvant chemotherapy.

A251 NON-ALCOHOLIC FATTY LIVER DISEASE AT A CANADIAN TERTIARY CARE CENTRE: RISK FACTORS AND SEVERITY OF DISEASE

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease worldwide with an increasing prevalence of 25-40%. Although the prevalence increases to 57.5-74% in obese patients, lean individuals also develop NAFLD. Patients are commonly asymptomatic and the diagnosis is often incidental or when progressed to cirrhosis. Once fibrosis has developed, the risk of cardiovascular and liver-related death increases exponentially. The increasing prevalence of NAFLD presents significant healthcare and economic consequences. The severity of NAFLD and its risk factors have been studied in various countries, which guide decisions on screening and management. Similar studies have not been performed in Canada. Purpose: To determine the severity of NAFLD in a tertiary care centre and associated risk factors. Method Retrospective review of patients with NAFLD diagnosed on ultrasound, or fibroscan from January 1, 2019 to December 31, 2021. Patients were 18 years or older and were excluded if they had co-existent liver disease, significant alcohol use or CAP &amp;lt;238. CAP and fibrosis scores were determined using transient elastography. Chi-square and multivariate analysis were performed for statistical analysis. Result(s): A total of 583 patients were included in the study; 312 (53.5%) were male and the mean age was 54.04 years. The majority of cases, 317 (56.8%), were diagnosed by ultrasound or CT scan and only 30 (5%) patients had a known family history of NAFLD. Lean-NAFLD (L-NAFLD) was present in 83 (15.2%) patients, overweight NAFLD (OW-NAFLD) 220 (40.2%), obese-NAFLD (OB-NAFLD) 206 (37.7%) and morbidly obese-NAFLD (MB-NAFLD) 38 (6.9%). The prevalence of T2DM was 28.6%, dyslipidemia 37.4%, hypertension 35.5%, coronary artery disease 6.2% and obstructive sleep apnea 6.7%. Risk factors for Stage 3 steatosis (CAP&amp;gt;290) included BMI&amp;gt;30 (2.84) and type 2 diabetes (OR 2.45), but not dyslipidemia, hypertension, age or gender. Type 2 diabetes, dyslipidemia, hypertension, BMI, gender and age were not significantly predictive of moderate steatosis (CAP 260-289). The proportion of patients with transient elastography scores of F2, F3, and F4 were 16.0%, 7.7%, and 11.0%, respectively. F2 and F3 scores were associated with T2DM (OR 1.94), BMI &amp;gt; 30 (OR 1.83, p&amp;lt;0.05) and age &amp;gt;60 (OR 1.90, p&amp;lt;0.05), but not dyslipidemia or hypertension. F4 scores were significantly associated with age &amp;gt; 60 (OR 1.89), T2DM (OR 2.60), dyslipidemia (OR 1.79), hypertension (OR 1.86) and BMI&amp;gt;30 (OR 2.54). Conclusion(s) Diabetes and BMI were associated with severe steatosis and fibrosis. Dyslipidemia and hypertension were only associated with advanced fibrosis. Our study demonstrates challenges in identification of early NAFLD given that metabolic syndrome factors were not associated with mild to moderate steatosis. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Development and validation of postoperative circulating tumor DNA combined with clinicopathological risk factors for recurrence prediction in patients with stage I-III colorectal cancer

BackgroundCirculating tumor DNA (ctDNA) detection following curative-intent surgery could directly reflect the presence of minimal residual disease, the ultimate cause of clinical recurrence. However, ctDNA is not postoperatively detected in ≥ 50% of patients with stage I-III colorectal cancer (CRC) who ultimately recur. Herein we sought to improve recurrence risk prediction by combining ctDNA with clinicopathological risk factors in stage I-III CRC.MethodsTwo independent cohorts, both consisting of early-stage CRC patients who underwent curative surgery, were included: (i) the discovery cohort (N = 124) with tumor tissues and postoperative plasmas for ctDNA determination; and (ii) the external validation cohort (N = 125) with available ctDNA results. In the discovery cohort, somatic variations in tumor tissues and plasmas were determined via a 733-gene and 127-gene next-generation sequencing panel, respectively.ResultsIn the discovery cohort, 17 of 108 (15.7%) patients had detectable ctDNA. ctDNA-positive patients had a significantly high recurrence rate (76.5% vs. 16.5%, P < 0.001) and short recurrence-free survival (RFS; P < 0.001) versus ctDNA-negative patients. In addition to ctDNA status, the univariate Cox model identified pathologic stage, lymphovascular invasion, nerve invasion, and preoperative carcinoembryonic antigen level associated with RFS. We combined the ctDNA and clinicopathological risk factors (CTCP) to construct a model for recurrence prediction. A significantly higher recurrence rate (64.7% vs. 8.1%, P < 0.001) and worse RFS (P < 0.001) were seen in the high-risk patients classified by the CTCP model versus those in the low-risk patients. Receiver operating characteristic analysis demonstrated that the CTCP model outperformed ctDNA alone at recurrence prediction, which increased the sensitivity of 2 year RFS from 49.6% by ctDNA alone to 87.5%. Harrell's concordance index, calibration curve, and decision curve analysis also suggested that the CTCP model had good discrimination, consistency, and clinical utility. These results were reproduced in the validation cohort.ConclusionCombining postoperative ctDNA and clinical risk may better predict recurrence than ctDNA alone for developing a personalized postoperative management strategy for CRC.

Relationship Between Liver Function Tests &amp; Cardiovascular Risk Factors in Stage 3-5 Pre-Dialysis Chronic Kidney Disease

Objectives: The main objective of this study was to evaluate the relation between liver function tests and biochemical cardiovascular risk factors in chronic kidney disease patients. Methodology: this study was conducted in Khyber Teaching Hospital Peshawar, from Ist May 2022 till 31st Oct, 2022. 250 patients in total were included in this study. All the people included in this study were chronic kidney disease patients at pre dialysis stage 3 to 5. Data collected included demographic information, liver function tests and biochemical cardiovascular risk factors. CKD-EPI equation was used to calculate glomerular filtration rate. Results: This study resulted in ALT being negatively correlated with C reactive protein and intact level of parathyroid hormone and positively correlated with glomerular filtration rate, triglyceride, calcifediol and albumin. Gamma-glutamyl transferase was negatively correlated with HDL cholesterol and positively correlated with glomerular filtration rate, triglycerides and C reactive protein. AST was negatively correlated with C reactive protein and intact level of parathyroid hormone and positively correlated with glomerular filtration rate, HDL cholesterol, albumin and calcifediol. In diabetic patients AST and ALT were positively correlated with glomerular filtration rate, additionally AST was also positively correlated with HDL cholesterol but negatively with intact parathyroid hormone. Gamma-glutamyl transferase had no correlation. In total population of the study and in diabetic group correlation analysis was run between glomerular filtration rate and biochemical cardiovascular risk factors, it resulted in GFR being negatively correlated with albuminuria, C reactive protein and intact parathyroid hormone and positively correlated with triglyceride, calcifediol and albumin. A partial correlation analysis, controlled for GFR, was also run between cardiovascular risk factors and LFTs. It resulted in no correlation between both. Practical implication: this study could be useful when planning the treatment of CKD patients with cardiovascular risk factors. Also in predicting the risk of cardiovascular disease in CKD patients based on the LFTs. It could also help initiate further reseach on related topics like the role of LFTs in predicting cardiovascular disease in CKD patients. Conclusion: this study concluded that relation between liver function tests and biochemical cardiovascular risk factors in chronic kidney disease patients could be the function of compromised glomerular filtration rate. Keywords: cardiovascular risk factors, chronic kidney disease, aspartate transaminase, gamma-glutamyl transferase, alanine transaminase

Relationship between liver function tests & cardiovascular risk factors in stage 3-5 pre-dialysis chronic kidney disease.

Cardiovascular disease (CVD) remains the leading cause of mortality among patients with chronic kidney disease (CKD). Liver function tests (LFTs) have emerged as markers of CVD risk in some population-based studies. Hence, in the present study the relation between LFTs and biochemical cardiovascular risk factors (CRFs) were evaluated in CKD patients. A total of 246 patients with stage 3-5 pre-dialysis CKD were enrolled. Demographics, LFTs [alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT)] and biochemical CRFs were recorded retrospectively. Glomerular filtration rate (GFR) was calculated using CKD-EPI equation. ALT was positively correlated with GFR, albumin, triglyceride and 25-hydroxyvitamin D and negatively correlated with CRP and intact parathyroid hormone (iPTH); AST was positively correlated with GFR, albumin, high-density lipoprotein cholesterol (HDL-C) and 25-hydroxyvitamin D and negatively correlated with CRP and iPTH; GGT was positively correlated with GFR, CRP and triglyceride and negatively correlated with HDL-C. In diabetic patients, ALT correlated positively with GFR; AST correlated positively with GFR and HDL-C, but correlated negatively with iPTH. In the correlation analysis between GFR and CRF, GFR was positively correlated with albumin, triglyceride and 25-hydroxyvitamin D and negatively correlated with CRP, iPTH and albuminuria in both total study population and diabetic group. A partial correlation analysis revealed no correlation between LFTs and CRFs after being controlled for GFR. The results of the present study suggest that the relationship between LFTs and biochemical CRFs seems to be a function of impaired GFR.

Determinants and Incidence of Chronic Kidney Disease with Tenofovir- Based Antiretroviral Therapy Regimens: A Cohort Study in HIV-Infected Adults in South China.

The data of the impact of tenofovir (TDF) on kidney damage in Chinese HIV-1 infected patients are limited. The study aims to evaluate the incidence and risk factors of stage 3 chronic kidney disease (CKD) and rapid kidney function decline (RKFD) among Chinese HIV-1 infected patients starting with a TDF-based regimen. We enrolled 797 TDF-initiated HIV-1-infected patients in a Chinese cohort. Kidney dysfunctions were defined as stage 3 CKD (eGFR < 60 mL/min/1.73 m2 during follow-up) and RKFD (eGFR decline > 10 mL/min/1.73 m2/year). A linear mixed-effects model was used to quantify the average eGFR change per 48 weeks. A generalized estimating equation regression analysis was conducted to determine the risk factors associated with renal dysfunction. The method of multiple imputations was used to reduce the bias caused by missing data. In this retrospective study, 14 (2%) patients experienced stage 3 CKD, and 272 (34%) individuals experienced RKFD during a median of 26 (IQR, 4-78; maximum 325) weeks follow-up period. The mean loss in eGFR per 48 weeks increased consistently over time, from -2.59 mL/min/1.73 m2 before 48 weeks to -17.61 mL/min/1.73 m2 after 288 weeks. For every 10 mL/min/1.73 m2 increase of eGFR, the risk of RKFD increased by 29% (95%CI: 18%, 40%). Each 10 years older and every 10 mL/min/1.73 m2 higher in baseline eGFR, the risk of stage 3 CKD increased to 1.56 (95% CI: 1.00, 2.43) and decreased by 65% (95% CI: 48%, 76%), respectively. Anemia and higher viral load were significantly associated with RKFD. The results were robust across a range of multiple imputation analyses. TDF-associated CKD is rare in HIV-1 infected Chinese adults. Longer TDF-exposed patients are more likely to have renal dysfunction, especially those with older age, anemia, lower baseline eGFR, and higher viral load.

Evaluation of Amide Proton Transfer-Weighted Imaging for Risk Factors in Stage I Endometrial Cancer: A Comparison With Diffusion-Weighted Imaging and Diffusion Kurtosis Imaging.

BackgroundEndometrial cancer (EC) is one of the most common gynecologic malignancies in clinical practice. This study aimed to compare the value of diffusion-weighted imaging (DWI), diffusion kurtosis imaging (DKI), and amide proton transfer-weighted imaging (APTWI) in the assessment of risk stratification factors for stage I EC including histological subtype, grade, stage, and lymphovascular space invasion (LVSI).MethodsA total of 72 patients with stage I EC underwent pelvic MRI. The apparent diffusion coefficient (ADC), mean diffusivity (MD), mean kurtosis (MK), and magnetization transfer ratio asymmetry (MTRasym at 3.5 ppm) were calculated and compared in risk groups with the Mann–Whitney U test or independent samples t-test. Spearman’s rank correlation was applied to depict the correlation of each parameter with risk stratification. The diagnostic efficacy was evaluated with receiver operating characteristic (ROC) curve analysis and compared using the DeLong test. A multivariate logistic regression was conducted to explore the optimal model for risk prediction.ResultsThere were significantly greater MTRasym (3.5 ppm) and MK and significantly lower ADC and MD in the non-adenocarcinoma, stage IB, LVSI-positive, high-grade, and non-low-risk groups (all p < 0.05). The MK and MTRasym (3.5 ppm) were moderately positively correlated with risk stratification as assessed by the European Society for Medical Oncology (EMSO) clinical practice guidelines (r = 0.640 and 0.502, respectively), while ADC and MD were mildly negatively correlated with risk stratification (r = −0.358 and −0.438, respectively). MTRasym (3.5 ppm), MD, and MK were identified as independent risk predictors in stage I EC, and optimal predictive performance was obtained with their combinations (AUC = 0.906, sensitivity = 70.97%, specificity = 92.68%). The results of the validation model were consistent with the above results, and the calibration curve showed good accuracy and consistency.ConclusionsAlthough similar performance was obtained with each individual parameter of APTWI, DWI, and DKI for the noninvasive assessment of aggressive behavior in stage I EC, the combination of MD, MK, and MTRasym (3.5 ppm) provided improved predictive power for non-low-risk stage I EC and may serve as a superior imaging marker.

Circulating tumor DNA is a prognostic marker of tumor recurrence in stage II and III colorectal cancer: multicentric, prospective cohort study (ALGECOLS)

BackgroundIn non-metastatic colorectal cancer (CRC), we evaluated prospectively the pertinence of longitudinal detection and quantification of circulating tumor DNA (ctDNA) as a prognostic marker of recurrence. MethodThe presence of ctDNA was assessed from plasma collected before and after surgery for 184 patients classified as stage II or III and at each visit during 3–4 years of follow-up. The ctDNA analysis was performed by droplet-based digital polymerase chain reaction, targeting mutation and methylation markers, blindly from the clinical outcomes. Multivariate analyses were adjusted on age, gender, stage, and adjuvant chemotherapy. ResultsBefore surgery, 27.5% of patients were positive for ctDNA detection. The rate of recurrence was 32.7% and 11.6% in patients with or without detectable ctDNA respectively (P = 0.001). Time to recurrence (TTR) was significantly shorter in patients with detectable ctDNA before (adjusted hazard ratio [HR] = 3.58, 95% confidence interval [CI] 1.71–7.47) or immediately after surgery (adjusted HR = 3.22, 95% CI 1.32–7.89). The TTR was significantly shorter in patients with detectable ctDNA during the early postoperative follow-up (1–6 months) (adjusted HR = 5, 95% CI 1.9–12.9). Beyond this period, ctDNA remained a prognostic marker with a median anticipated diagnosis of recurrence of 13.1 weeks (interquartile range 28 weeks) when compared to imaging follow-up. The rate of ctDNA+ might be underestimated knowing that consensus pre-analytical conditions were not described at initiation of the study. ConclusionThis prospective study confirms the relevance of ctDNA as a recurrence risk factor in stage II and III CRC before surgery and as a marker of minimal residual disease after surgery that may predict recurrence several months before imaging techniques.

30 Risk Factors for Stage III Necrotizing Enterocolitis in Very Low Birth Weight Neonates – A retrospective case-control study

Abstract Primary Subject area Neonatal-Perinatal Medicine Background Stage III necrotizing enterocolitis (NEC-III) is a serious intestinal inflammatory disease in neonates, with high case fatality rate and significant morbidities including need for surgical intervention. Research focusing on risk factors for the development of NEC-III are lacking. Objectives To determine the risk factors for NEC-III and its outcomes among neonates born under 33 weeks gestational age (GA). Design/Methods This was a single-centre retrospective case-control study of preterm neonates born under 33 weeks GA who were admitted to Stollery Children’s Hospital neonatal intensive care unit (NICU), Edmonton, Alberta, between January 2015 and December 2018. NEC-III cases were compared with Stage II NEC (NEC-II) and matched with 2-4 non-NEC controls by GA ± 1 week and date of birth within 3 months. Univariate and multivariate analysis compared the risk factors for NEC-III, adjusting for GA, birth weight, and sex. Results Out of 1360 babies born &amp;lt;33weeks, 71(5.2%) had NEC-II and above during the study period (Figure 1). NEC-III constituted 46% of the total number of NEC cases. Average age of onset of NEC-III was 13.7 days versus 23.9 days for NEC-II (p=0.01). Neonates with NEC-III were of lower GA (25.4weeks) compared to NEC-II(27.3 weeks) and non-NEC (26 weeks), (p=0.0008), had higher severity of illness with Score for Neonatal Acute Physiology Perinatal Extension-II (SNAPPE-II score) of 47.5 versus 28.4 for NEC-II and 37 for non-NEC ( p=0.003), spent more days on vasoactive agents (3.7 days versus 1.1 days and 1.8 days for NEC-II and non-NEC respectively; p=0.05). There was a trend towards lower Apgar score &amp;lt;7 at 10 mintues in NEC-III versus non-NEC (AOR 2.59, 95% CI [0.88-7.67]; p=0.085). Death or short bowel syndrome was higher for NEC III (AOR 12.4, 95% CI [1.16-132.28]; p=0.037). Conclusion In this case-control study of neonates born under 33 weeks GA, after adjustment for known confounders, duration of UAC and prolonged rupture of membranes were significantly associated with increased incidence of NEC-III. Composite outcome of mortality or short bowel syndrome were higher in NEC-III.

HER2 positivity as a biomarker for poor prognosis and unresponsiveness to anti-EGFR therapy in colorectal cancer.

To investigate the role of HER2 positivity in prognosis and unresponsiveness to anti-EGFR therapy for colorectal cancer. Patients who underwent primary CRC tumor resection were included. HER2 status of CRC was confirmed by immunohistochemistry and fluorescence in situ hybridization tests. Comparison of survival analysis between HER2 positivity and negativity was evaluated by a stratified log-rank test and summarized with the use of Kaplan-Meier and Cox proportional hazards methods. The treatment effects of cetuximab were further compared in full subgroup analyses. 1240 patients were enrolled, including 763 with stage I-III CRC and 477 with stage IV CRC. 57 (4.6%) CRC patients presented HER2 positivity in the entire cohort. The survival analysis showed that patients with HER2 positivity had significantly worse disease-free survival and overall survival in stage III and IV CRC. The multivariable analysis also confirmed that HER2 positivity was a significantly independent risk factor in stage III and IV CRC. Univariate and multivariable survival analysis showed no prognostic significance of HER2 positivity in stage I-II CRC patients. Prespecified subgroup analysis showed no favorable trends in progression-free survival and overall survival for cetuximab in the patients with HER2 positivity, KRAS/NRAS/BRAF wild-type metastatic CRC (interaction P values = 0.005 and 0.014). For stage III and IV CRC patients, HER2 positivity was confirmed as an independent prognostic risk factor. It could help predict the unresponsiveness to anti-EGFR therapy for metastatic CRC.

Brief report: Lymph node morphology in stage II colorectal cancer.

Colorectal cancer is one of the leading causes of cancer-associated morbidity and mortality worldwide. The local anti-tumour immune response is particularly important for patients with stage II where the tumour-draining lymph nodes have not yet succumbed to tumour spread. The lymph nodes allow for the expansion and release of B cell compartments such as primary follicles and germinal centres. A variation in this anti-tumour immune response may influence the observed clinical heterogeneity in stage II patients. The aim of this study was to explore tumour-draining lymph node histomorphological changes and tumour pathological risk factors including the immunomodulatory microRNA-21 (miR-21) in a small cohort of stage II CRC. A total of 23 stage II colorectal cancer patients were included. Tumour and normal mucosa samples were analysed for miR-21 expression levels and B-cell compartments were quantified from Haematoxylin and Eosin slides of lymph nodes. These measures were compared to clinicopathological risk factors such as perforation, bowel obstruction, T4 stage and high-grade. We observed greater Follicle density in patients with a lower tumour T stage and higher germinal centre density in patients with higher pre-operative carcinoembryonic antigen levels. Trends were also detected between tumours with deficiency in mismatch repair proteins, lymphatic invasion and both the density and size of B-cell compartments. Lastly, elevated tumour miR-21 was associated with decreased Follicle and germinal centre size. Variation in B-cell compartments of tumour-draining lymph nodes is associated with clinicopathological risk factors in stage II CRC patients.

Completeness and accuracy of the registration of recurrences in the Swedish Colorectal Cancer Registry (SCRCR) and an update of recurrence risk in colon cancer

Background The completeness and accuracy of the registration of synchronous metastases and recurrences in the Swedish Colorectal Cancer Registry has not been investigated. Knowing how accurate these parameters are in the registry is a prerequisite to adequately measure the current recurrence risk. Methods All charts for patients diagnosed with stage I–III colorectal cancer (CRC) in two regions were reviewed. In one of the regions, all registrations of synchronous metastases were similarly investigated. After the database had been corrected, recurrence risk in colon cancer was calculated stratified by risk group as suggested by ESMO in 2020. Results In patients operated upon more than five years ago (N = 1235), there were 20 (1.6%) recurrences not reported. In more recent patients, more recurrences were unreported (4.0%). Few synchronous metastases were wrongly registered (3.6%) and, likewise, few synchronous metastases were not registered (about 1%). The five-year recurrence risk in stage II was 6% for low-risk, 11% for intermediate risk, and 23% for high-risk colon cancer patients. In stage III, it was 25% in low- and 45% in high-risk patients. Incorporation of risk factors in stage III modified the risks substantially even if this is not considered by ESMO. Adjuvant chemotherapy lowered the risk in stage III but not to any relevant extent in stage II. Conclusion The registration of recurrences in the registry after 5 years is accurate to between 1 and 2% but less accurate earlier. A small number of unreported recurrences and falsely reported recurrences were discovered in the chart review. The recurrence risk in this validated and updated patient series matches what has been recently reported, except for the risk of recurrence in stage II low risk colon cancers which seem to be even a few percentage points lower (6 vs. 9%).

Impact of Lymphovascular Invasion in Patients With Stage II Colorectal Cancer: A Propensity Score-matched Study.

Whether lymphovascular invasion (LVI) is a high-degree risk factor in stage II colorectal cancer has not been fully clarified, as different results have been reported in the literature. If LVI is a risk factor, postoperative chemotherapy may be recommended. The purpose of this study was to evaluate the impact of lymphovascular invasion on disease recurrence and patient prognosis in conjunction with stage II colorectal cancer (CRC). A total of 636 patients with stage II CRC, each undergoing radical resection between April 2007 and December 2015, were selected for the study. Subjects with or without venous or lymphatic invasion were assigned to positive and negative groups, respectively. We then compared overall survival (OS) and disease-free survival (DFS) using propensity score matching. After matching (n=226, each group), OS and DFS were found to be significantly lower (OS: p=0.047; DFS: p=0.004) in patients positive (vs. negative) for venous invasion. However, the same was not true of lymphatic invasion. After matching, positive and negative groups (n=92, each) did not significantly differ in terms of OS (p=0.951) or DFS (p=0.258). In patients with stage II CRC, venous invasion proved to be a significant high-degree risk factor that may warrant adjuvant chemotherapy.